Some neurons in the lamprey eels heal remarkable well, but others don’t. Now researchers have uncovered a single factor that may determine life or death in these cells, the buildup of the protein synuclein.

The eels have it—at least when it comes to understanding why brain cells die
after a spinal cord injury.

Using lamprey eels, Petromyzon marinus, scientists have shown that
after injury, the brain cells that deteriorate and die tend to build up more
of the protein synuclein compared to the cells that survive. This protein
accumulation is similar to what occurs during neurodegenerative diseases
such as Parkinson’s disease and could be instrumental in the development of
treatments.

This image shows synuclein expression in the brain of a lamprey. Credit: David Busch, UT-Austin.

"Synuclein accumulation is a pretty reliable indicator of neurons that
are dying after spinal cord injury," said Jennifer Morgan, a
neurobiologist at the University of Texas, Austin and a co-author of the new
study describing the discovery, which was published in the Journal of
Comparative Neurology (1). This correlation, however, does not
necessarily mean that synuclein build-up is the cause of cell death.

She and fellow UT-Austin neuroscientist David Busch identified the link
between synuclein build-up and cell death using the "subset of very
large, identifiable neurons," called reticulospinal, or RS neurons in
lamprey eels. Because these giant neurons are located in similar spots in
every lamprey brain, scientists can easily study them in a large number of
animals.

While many of the lamprey eel’s RS neurons are "reproducibly good"
at surviving an injury and regenerating their axons, others die. "By
using the lamprey model, we can examine the molecular events that are
happening in vivo in 'good survivors' versus 'poor survivors' and how these
molecular events impact the regeneration process," Morgan said.

In the experiment, Morgan severed a group of eels' spinal cords at their fifth
gill. Using Nissl and Fluoro-Jade C staining, the scientists monitored these
RS neurons after injury. After week one, many of the neurons remained
healthy, but by week three they began to degenerate. After week 11, 30% of
all of the RS neurons in injured lampreys had deteriorated.

Next, the researchers used a synuclein antibody and immunofluorescence to
measure the build up of synuclein in the RS neurons. The results showed that
the greatest protein build-up was in the "poor survivor" neurons.

"The link between cell-specific synuclein accumulation and
neurodegeneration after spinal cord injury had not been made before this
study," Morgan said. Because synuclein accumulation is a bioindicator
of imminent neuronal death in Parkinson’s disease, strategies to diagnose
and treat Parkinson’s could potentially be effective in patients with spinal
cord injuries.

Next, Morgan will attempt to disrupt synuclein accumulation post injury to
further explore its relationship to neurodegeneration. "Spinal cord
injury will be an area of research and medicine where we will continue to
see significant progress over the next decade," said Morgan.